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McCune-Albright syndrome (MAS) is classically defined by the clinical triad of fibrous dysplasia of bone (FD), café-au-lait skin spots, and precocious puberty (PP).
ORPHA:562Classification level: Disorder
It is a rare disease with an estimated prevalence of between 1/100,000 and 1/1,000,000.
FD can involve single or multiple skeletal sites and presents with a limp and/or pain, and, occasionally, a pathologic fracture. Scoliosis is common and may be progressive. In addition to PP (vaginal bleeding or spotting and early development of breast tissue in girls, testicular and penile enlargement and precocious sexual behavior in boys), other hyperfunctioning endocrinopathies may occur including hyperthyroidism, growth hormone excess, Cushing syndrome, and renal phosphate wasting. Café-au-lait spots usually appear in the neonatal period, but it is most often PP or FD that brings the child to medical attention. Renal involvement is seen in approximately 50% of the patients with MAS.
The disease results from somatic mutations of the GNAS gene, specifically mutations in the cAMP-regulating protein, Gs alpha. The extent of the disease is determined by the proliferation, migration and survival of the cell in which the mutation spontaneously occurs during embryonic development.
Diagnosis of MAS is usually established on clinical grounds. Plain radiographs are often sufficient to make the diagnosis of FD but biopsy of FD lesions can be used for confirmation. The evaluation of patients with MAS should be guided by knowledge of the spectrum of tissues that may be involved, with specific testing for each. Genetic testing is possible, but is not routinely available.
Differential diagnoses include neurofibromatosis, osteofibrous dysplasia, non-ossifying fibromas, idiopathic central precocious puberty, and ovarian neoplasm (see these terms).
Although MAS in not hereditary, genetic counseling should be offered.
Management and treatment
Treatment is dictated by the tissues affected, and the extent to which they are affected. Some forms of surgical interventions may be indicated for treatment of craniofacial and skeletal abnormalities associated with FD (progressive visual disturbance, severe pain, severe disfigurement), as well as in the management of MAS-associated endocrinopathies and malignancies. Bisphosphonates are frequently used in the treatment of FD. Strengthening exercises are recommended to help maintain the musculature around the FD bone and minimize the risk of fracture. Treatment of all endocrinopathies is required.
MAS is rarely associated with malignancy. Malignant transformation of FD lesions occurs in probably less than 1% MAS patients.